Myocardial blood flow quantitation with the novel F-18 Flurpiridaz PET imaging tracer PROECT SUMMARY Coronary artery disease (CAD) is the single largest cause of death in the United States. Prevention, early diagnosis, and treatment of CAD are essential to reduce the mortality. Noninvasive assessments of regional myocardial blood flow at rest and during stress have proved valuable for early diagnosis of CAD. These assessments can be with a radioactive-labeled myocardial perfusion imaging (MPI) agent using Single Photon Emission Computed Tomography (SPECT) or Positron Emission Tomography (PET), Flurpiridaz F-18 is a novel, new PET myocaridal perfusion imaging (MPI) agent labeled with 18F. This agent is a structural analog of pyridaben, a known mitochondrial complex 1 (MC-1) inhibitor. As mitochondria constitute 20 to 30% of the myocardial intracellular volume, molecules that target mitochondrial proteins will be enriched and retained selectively in the myocardium. In pre-clinical studies, flurpiridaz has shown a higher first pass extraction fraction than Tl-201 and Tc-99m-sestamibi at high flow rates. Thus, flurpiridaz can provide the opportunity to perform myocardial perfusion imaging with the improved resolution and quantification afforded by PET. PET has several technical advantages over SPECT including: 1) routine measured attenuation correction, which decreases the number of false-positives, thereby increasing specificity; 2) high spatial and contrast resolution that allows for improved detection of small perfusion defects which decreases the number of false-negatives, thereby increasing sensitivity; and 3) high temporal resolution that allows fast dynamic imaging of tracer kinetics. The latter makes absolute quantification of MBF possible, which has been shown to improve sensitivity for detection of multi-vessel disease and evaluation of conditions that diffusely affect coronary circulation. Flurpiridaz also could provide improved clinical utility and ease of use because of the longer half-life (109 minutes) of an 18 F-based agent compared to current PET MPI agents (82rubidium (Rb-82) chloride, 13nitrogen (N-13) ammonia, and 15oxygen (O-15) water) that makes delivery of unit doses from regional cyclotrons quite feasible which could not be achieved with the current shorter half-live agents. There is a need to optimize the acquisition and processing protocols in order to take full advantage of this ideal MPI agent. The clinical and technical research project proposed in this SBIR submission will address this optimization for the flurpiridaz imaging agent. This Phase II submission is following the nearly completed SBIR Phase I grant 1R43HL123069-01 which was awarded on June 24, 2014. Our long-term objective for this project is to improve patient care and outcomes through increased diagnostic accuracy of coronary heart disease (CHD), maximize clinical diagnostic confidence, and reduce costs by: 1) optimizing the method for flow calculation, 2) establishing quality control procedures and output for evaluation of the study, 3) standardizing the acquisition and processing protocols for Flurpiridaz F-18, 4) developing both relative and absolute quantitation, plus measurements of myocardial blood flow (MBF) and coronary flow reserve (CFR) using the novel new cardiac imaging agent Flurpiridaz F-18, 5) developing an innovative Decision Support System (DSS) system as part of the relative quantitation which will drive an automatic, structured, natural language reporting system thereby increasing clinical confidence and reducing time/cost, and 6) maximizing the availability of these benefits by incorporating all of this into a widely utilized and widely available commercial product, the Emory Cardiac Toolbox(tm) (ECTb).